View source for 6nhy


==Structure of the transmembrane domain of the Death Receptor 5 mutant (G217Y) - Trimer Only==
<StructureSection load='6nhy' size='340' side='right'caption='[[6nhy]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6nhy]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NHY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NHY FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6nhy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nhy OCA], [https://pdbe.org/6nhy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nhy RCSB], [https://www.ebi.ac.uk/pdbsum/6nhy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nhy ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/TR10B_HUMAN TR10B_HUMAN] Defects in TNFRSF10B may be a cause of head and neck squamous cell carcinomas (HNSCC) [MIM:[https://omim.org/entry/275355 275355]; also known as squamous cell carcinoma of the head and neck.
== Function ==
[https://www.uniprot.org/uniprot/TR10B_HUMAN TR10B_HUMAN] Receptor for the cytotoxic ligand TNFSF10/TRAIL. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Promotes the activation of NF-kappa-B. Essential for ER stress-induced apoptosis.<ref>PMID:15322075</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Receptor clustering on the cell membrane is critical in the signaling of many immunoreceptors, and this mechanism has previously been attributed to the extracellular and/or the intracellular interactions. Here, we report an unexpected finding that for death receptor 5 (DR5), a receptor in the tumor necrosis factor receptor superfamily, the transmembrane helix (TMH) alone in the receptor directly assembles a higher-order structure to drive signaling and that this structure is inhibited by the unliganded ectodomain. Nuclear magnetic resonance structure of the TMH in bicelles shows distinct trimerization and dimerization faces, allowing formation of dimer-trimer interaction networks. Single-TMH mutations that disrupt either trimerization or dimerization abolish ligand-induced receptor activation. Surprisingly, proteolytic removal of the DR5 ectodomain can fully activate downstream signaling in the absence of ligand. Our data suggest a receptor activation mechanism in which binding of ligand or antibodies to overcome the pre-ligand autoinhibition allows TMH clustering and thus signaling.

Higher-Order Clustering of the Transmembrane Anchor of DR5 Drives Signaling.,Pan L, Fu TM, Zhao W, Zhao L, Chen W, Qiu C, Liu W, Liu Z, Piai A, Fu Q, Chen S, Wu H, Chou JJ Cell. 2019 Mar 7;176(6):1477-1489.e14. doi: 10.1016/j.cell.2019.02.001. Epub 2019, Feb 28. PMID:30827683<ref>PMID:30827683</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6nhy" style="background-color:#fffaf0;"></div>

==See Also==
*[[TRAIL|TRAIL]]
*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chen W]]
[[Category: Chou JJ]]
[[Category: Fu T]]
[[Category: Liu Z]]
[[Category: Pan L]]
[[Category: Piai A]]
[[Category: Wu H]]
[[Category: Zhao L]]